title: Different immunity elicited by recombinant H5N1 hemagglutinin proteins containing pauci-mannose, high-mannose, or complex type N-glycans.
abstract: Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality. A safe and effective H5N1 vaccine is urgently needed to reduce the pandemic potential. Hemagglutinin (HA), a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development. In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9) cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic) and mammalian cells (CHO). While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins. Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge. The results are highly relevant to issues that should be considered in the production of fragment vaccines.
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Lin
authors.forename: Jia-Tsrong
authors.initials: JT
authors.lastname: Jan
authors.forename: Ben
authors.initials: B
authors.lastname: Dionne
authors.forename: Michael
authors.initials: M
authors.lastname: Butler
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Suh-Chin
authors.initials: SC
authors.lastname: Wu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000921:Antibody-Producing Cells / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology; D016466:CHO Cells; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006031:Glycosylation; D006388:Hemagglutinins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008351:Mannans / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D061987:Sf9 Cells; D018411:Spodoptera; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006388:Hemagglutinins; D007132:Immunoglobulin Isotypes; D007252:Influenza Vaccines; D008351:Mannans; D014764:Viral Proteins